A pilot trial of topiramate for the treatment of cocaine dependence
A pilot trial of topiramate for the treatment of cocaine dependence
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DOI：
10.1016/j.drugalcdep.2004.03.008
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发表时间：
2004-09-06
影响因子：
4.2
通讯作者：
O'Brien, CP
中科院分区：
文献类型：
--
作者：
Kampman, KM;Pettinati, H;O'Brien, CP
背景：GABA 能和谷氨酸能神经元似乎都是大脑奖赏系统的重要调节剂，影响 GABA 和谷氨酸能神经传递的药物可能会降低可卡因的奖赏特性并减少对可卡因的渴望。托吡酯是一种抗惊厥药，可提高大脑 GABA 水平，促进 GABA 能神经传递并抑制 AMPA/红藻氨酸受体的谷氨酸活性。因此，它可能有助于治疗可卡因依赖。方法：在一项为期 13 周、双盲、安慰剂对照的试点试验（n = 40）中测试了托吡酯对可卡因依赖的疗效。托吡酯在 8 周内逐渐滴定至每天 200 毫克的剂量。主要结果指标是通过每周两次尿液苯甲酰爱康宁测试（UBT）验证可卡因戒断情况。结果：百分之八十二的受试者完成了试验。使用 GEE 模型对 UBT 进行的分析表明，第 8 周后，当剂量滴定完成时，与安慰剂治疗的受试者相比，托吡酯治疗的受试者更有可能戒除可卡因（Z = 2.67，P = 0.01）。托吡酯治疗的受试者也更有可能连续戒除可卡因 3 周（chi(2) = 3.9，d.f. = 1，P = 0.05）。结论：托吡酯可能有效治疗可卡因依赖。 (C) 2004 Elsevier Ireland Ltd. 保留所有权利。
Background: Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence. Methods: The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT). Results: Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi(2) = 3.9, d.f. = 1, P = 0.05). Conclusion: Topiramate may be effective for the treatment of cocaine dependence. (C) 2004 Elsevier Ireland Ltd. All rights reserved.